Inflammation is a determinant of atherosclerotic plaque rupture, the event leading to most myocardial infarctions and strokes. Although conventional imaging techniques identify the site and severity of luminal stenosis, the inflammatory status of the plaque is not addressed. Positron emission tomography imaging of atherosclerosis using the metabolic marker fluorodeoxyglucose allows quantification of arterial inflammation across multiple vessels. This review sets out the background and current and potential future applications of this emerging biomarker of cardiovascular risk, along with its limitations.

Atherosclerosis imaging with 18 F-FDG PET is useful for tracking inflammation within plaque and monitoring the response to drug therapy. Short-term reproducibility of this technique in peripheral artery disease has not been assessed, and the optimal method of 18 F-FDG quantification is still debated. We imaged 20 patients with vascular disease using 18 F-FDG PET twice, 14 d apart, and used these data to assess reproducibility measures and compare 2 methods of 18 F-FDG uptake measurement. We also reviewed the literature on quantification methods to determine the optimal measures of arterial 18 F-FDG uptake for future studies. Methods: Twenty patients with vascular disease underwent PET/CT of the iliac, femoral, and carotid arteries 90 min after 18 F-FDG administration. In 19 patients, repeat testing was performed at 2 wk. Coregistration and attenuation correction were performed with CT. Vessel 18 F-FDG uptake was measured as both the mean and maximum blood-normalized standardized uptake value (SUV), known as the target-to-background ratio (TBR). We assessed interscan, interobserver, and intraobserver agreement. Results: Nineteen patients completed both imaging sessions. The carotid and peripheral arteries all have excellent short-term reproducibility of the 18 F-FDG signal, with intraclass correlation coefficients all greater than 0.8 for all measures of reproducibility. Both mean and maximum TBR measurements for quantifying 18 F-FDG uptake are equally reproducible. 18 F-FDG uptake was significantly higher in the carotid arteries than in both iliac and femoral vessels (P , 0.001 for both). Conclusion: We found that both mean and maximum TBR in the carotid, iliac, and femoral arteries were highly reproducible. We suggest the mean TBR be used for tracking systemic arterial therapies, whereas the maximum TBR is optimal for detecting and monitoring local, plaque-based therapy.

Spontaneous change in plaque FDG uptake is low over 2 weeks, with favorable inter- and intraobserver agreement. Power calculations suggest that drug studies using FDG-PET imaging would require few subjects compared with other imaging modalities. This study strengthens the case for FDG-PET as a noninvasive plaque imaging technique.

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Objective-The association of inflammatory cells and neovessels in atherosclerosis is considered a histological hallmark of high-risk active lesions. Therefore, the development and validation of noninvasive imaging techniques that allow for the detection of inflammation and neoangiogenesis in atherosclerosis would be of major clinical interest. Our aim was to test 2 techniques, black blood dynamic contrast enhanced MRI (DCE-MRI) and 18-fluorine-fluorodeoxyglucose (18F-FDG) PET, to quantify inflammation expressed as plaque neovessels content in a rabbit model of atherosclerosis. Methods and Results-Atherosclerotic plaques were induced in the aorta of 10 rabbits by a combination of 2 endothelial abrasions and 4 months hyperlipidemic diet. Six rabbits underwent MRI during the injection of Gd-DTPA, whereas 4 rabbits were imaged after injection of 18F-FDG with PET. We found a positive correlation between neovessels count in atherosclerotic plaques and (1) Gd-DTPA uptake parameters evaluated by Pϭ0.016) and (2) 18F-FDG uptake evaluated by PET (rϭ0.5, Pϭ0.103 after clustered robust, Huber-White, standard errors analysis). Key Words: atherosclerosis Ⅲ inflammation Ⅲ neovessels Ⅲ MRI Ⅲ PET N eovascularization is one of the hallmarks of high-risk/ vulnerable atherosclerotic lesions. It is characterized by the formation of new capillaries in the atherosclerotic plaque, and it is usually considered a response to the hypoxic conditions within the vessel wall during plaque growth. 1 However, more recent reports have identified hypoxia independent pathways of angiogenesis mediated primarily by inflammation 2,3 : these studies have highlighted the link between the presence of neovessels, the extravasation and activation of inflammatory cells, and lipid deposition in the vessel wall. Neovessels seem to play a key role in the progression of atherosclerotic plaques and plaque rupture. 1 From those reports it appears that the presence and extent of neovessels and inflammation in atherosclerotic plaques can be considered a marker of risk associated with the lesion. Therefore it would be of clinical relevance to develop techniques capable of quantifying the degree of plaque inflammation in a noninvasive and reliable manner. DCE-MRI is an imaging technique extensively used to study the vascularity of tumors. 4 This technique takes advantage of the administration of clinically-available contrast agents (ie, Gadolinium (Gd)-chelates) to quantify the extent of tumor blood supply and its associated physiological characteristics, such as permeability surface area product, extraction fraction, and blood flow. Recent studies on human carotid atherosclerotic plaques have shown that several gadolinium uptake parameters, evaluated by kinetic modeling 5 of DCE-MRI bright blood acquisitions, correlate with the extent of plaque vascularity and macrophage burden (confirmed by staining of histological specimens). 6,7 However, the use of the bright blood DCE technique makes it intrinsically difficult to reliably delineate the vessel lumen from the w...

Background Fluorodeoxyglucose positron emission tomography (FDG PET) imaging of atherosclerosis has been used to quantify plaque inflammation and to measure the effect of plaque stabilizing drugs. Here we explore how atherosclerotic plaque inflammation varies across arterial territories and how it relates to arterial calcification. We also test the hypotheses that the degree of local arterial inflammation measured by PET is correlated with the extent of systemic inflammation and presence of risk factors for vascular disease. Methods and Results Forty-one subjects underwent vascular PET/CT imaging with FDG. All had either vascular disease or multiple risk factors for it. Forty subjects underwent carotid imaging, twenty-seven underwent aortic, twenty-four iliac and thirteen femoral imaging. Thirty-three subjects had a panel of biomarkers analyzed. We found strong associations between FDG uptake in neighboring arteries (left vs. right carotid r=0.91, p<0.001, ascending aorta vs. aortic arch r=0.88, p<0.001). Calcification and inflammation rarely overlapped within arteries – carotid artery FDG uptake vs. calcium score r=−0.42, p=0.03). Carotid artery FDG uptake was greater in those with a history of coronary artery disease (target to background ratio (TBR) 1.83 vs. 1.61, p<0.01), and in males vs. females (TBR 1.83 vs. 1.63, p<0.05). Similar findings were also noted in the aorta and iliac arteries. Subjects with the highest levels of FDG uptake also had the greatest concentrations of inflammatory biomarkers: descending aorta TBR vs. matrix metalloproteinase 3 (MMP 3): r=0.53, p=0.01 and carotid TBR vs. MMP 9: r=0.50, p=0.01. Non-significant positive trends were seen between FDG uptake and levels of interleukin 18, fibrinogen and C-reactive protein. Finally, we found that the atheroprotective biomarker adiponectin was negatively correlated with the degree of arterial inflammation in the descending aorta: r=−0.49, p=0.03). Conclusions This study shows that FDG PET imaging can increase our knowledge of how atherosclerotic plaque inflammation relates to calcification, serum biomarkers and vascular risk factors. Plaque inflammation and calcification rarely overlap, supporting the theory that calcification represents a late, burnt-out stage of atherosclerosis. Inflammation in one arterial territory is associated with inflammation elsewhere, and the degree of local arterial inflammation is reflected in the blood levels of several circulating biomarkers. We suggest that FDG PET imaging could be used as a surrogate marker of both atherosclerotic disease activity and drug effectiveness. Prospective, event driven studies are now underway to determine the role of this technique in clinical risk prediction.

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